With the dramatic reduction in the cost of whole genome sequencing (WGS), genomic data are becoming increasingly available and have the potential to advance public health and promote personalized medicine. However, human genomic data usually carry sensitive personal information making data owners cautious about sharing it and genomic privacy is emerging as a big challenge for the entire biomedical community. In this proposal, we will develop novel methods for genomic privacy protection, which will facilitate genomic research. Our first aim is to develop privacy-preserving and efficiency-oriented computational models for processing, sharing, and storing genomic data in a cloud-based environment. This aim relies on scalable cryptographic techniques, joint compression, and encryption schemes, as well as leverage of high-performance computing architecture to achieve privacy-preserving analysis and storage efficiency in the cloud. The second aim is to develop trustworthy computational models that enable researchers to analyze distributed genomic data without requiring patient-level data exchange. These aims are devoted to the mission of the National Human Genome Research Institute (NHGRI) to develop resources and technology that will accelerate genome research and its application to human health. The NIH Pathway to Independence Award provides a great opportunity for the applicant to complement his computer engineering background with biomedical knowledge, and specialized training in genomic analysis, genomic privacy, as well as high-performance computing. It will also allow him to investigate new techniques to advance genomic privacy protection. The success of the proposed project will help his long-term career goal of obtaining a faculty position at a biomedical informatics program at a major US research university and conduct independently funded research in the field of genome privacy.